RESUMO
BACKGROUND: Duchenne muscular dystrophy (DMD) is a severe form of muscular dystrophy without an effective treatment, caused by mutations in the DMD gene, leading to the absence of dystrophin. DMD results in muscle weakness, loss of ambulation, and death at an early age. Metabolomics studies in mdx mice, the most used model for DMD, reveal changes in metabolites associated with muscle degeneration and aging. In DMD, the tongue muscles exhibit unique behavior, initially showing partial protection against inflammation but later experiencing fibrosis and loss of muscle fibers. Certain metabolites and proteins, like TNF-α and TGF-ß, are potential biomarkers for dystrophic muscle characterization. METHODS: To investigate disease progression and aging, we utilized young (1 month old) and old (21-25 months old) mdx and wild-type tongue muscles. Metabolite changes were analyzed using 1H nuclear magnetic resonance, while TNF-α and TGF-ß were assessed using Western blotting to examine inflammation and fibrosis. Morphometric analysis was conducted to assess the extent of myofiber damage between groups. RESULTS: The histological analysis of the mid-belly tongue showed no differences between groups. No differences were found between the concentrations of metabolites from wild-type or mdx whole tongues of the same age. The metabolites alanine, methionine, and 3-methylhistidine were higher, and taurine and glycerol were lower in young tongues in both wild type and mdx (p < 0.001). The metabolites glycine (p < 0.001) and glutamic acid (p = 0.0018) were different only in the mdx groups, being higher in young mdx mice. Acetic acid, phosphocreatine, isoleucine, succinic acid, creatine, and the proteins TNF-α and TGF-ß had no difference in the analysis between groups (p > 0.05). CONCLUSIONS: Surprisingly, histological, metabolite, and protein analysis reveal that the tongue of old mdx remains partially spared from the severe myonecrosis observed in other muscles. The metabolites alanine, methionine, 3-methylhistidine, taurine, and glycerol may be effective for specific assessments, although their use for disease progression monitoring should be cautious due to age-related changes in the tongue muscle. Acetic acid, phosphocreatine, isoleucine, succinate, creatine, TNF-α, and TGF-ß do not vary with aging and remain constant in spared muscles, suggesting their potential as specific biomarkers for DMD progression independent of aging.
Assuntos
Distrofia Muscular de Duchenne , Camundongos , Animais , Distrofia Muscular de Duchenne/genética , Fator de Necrose Tumoral alfa/genética , Creatina , Camundongos Endogâmicos mdx , Fosfocreatina , Glicerol , Isoleucina , Fibras Musculares Esqueléticas , Metionina , Racemetionina , Ácido Acético , Alanina , Progressão da DoençaRESUMO
Creatine (Cr) and phosphocreatine (PCr) are physiologically essential molecules for life, given they serve as rapid and localized support of energy- and mechanical-dependent processes. This evolutionary advantage is based on the action of creatine kinase (CK) isozymes that connect places of ATP synthesis with sites of ATP consumption (the CK/PCr system). Supplementation with creatine monohydrate (CrM) can enhance this system, resulting in well-known ergogenic effects and potential health or therapeutic benefits. In spite of our vast knowledge about these molecules, no integrative analysis of molecular mechanisms under a systems biology approach has been performed to date; thus, we aimed to perform for the first time a convergent functional genomics analysis to identify biological regulators mediating the effects of Cr supplementation in health and disease. A total of 35 differentially expressed genes were analyzed. We identified top-ranked pathways and biological processes mediating the effects of Cr supplementation. The impact of CrM on miRNAs merits more research. We also cautiously suggest two dose-response functional pathways (kinase- and ubiquitin-driven) for the regulation of the Cr uptake. Our functional enrichment analysis, the knowledge-based pathway reconstruction, and the identification of hub nodes provide meaningful information for future studies. This work contributes to a better understanding of the well-reported benefits of Cr in sports and its potential in health and disease conditions, although further clinical research is needed to validate the proposed mechanisms.
Assuntos
Creatina/administração & dosagem , Perfilação da Expressão Gênica , Genômica/métodos , Desempenho Físico Funcional , Animais , Creatina/metabolismo , Creatina Quinase/metabolismo , Suplementos Nutricionais , Metabolismo Energético , Estudo de Associação Genômica Ampla , Humanos , Camundongos , Proteínas Quinases Ativadas por Mitógeno , Proteínas de Transporte de Neurotransmissores , Fosfocreatina/metabolismo , Transdução de SinaisRESUMO
O objetivo do estudo foi realizar um breve comunicado sobre a adoção da densidade com uma nova métrica de quantificação de cargas no treinamento de força. Descrevemos como quantificá-la e destacamos as possíveis implicações da sua manipulação. Uma vez que considera o intervalo de recuperação entre as séries - onde podem ocorrer processos metabólicos importantes, como a ressíntese de fosfocreatina - a densidade pode ser um parâmetro representativo da magnitude do estresse metabólico induzido pelas sessões. Recomendamos que treinadores e pesquisadores da área de ciências do esporte passem a reportar quantificar e reportar a densidade dos treinos. Técnicas de treinamento que manipulam as pausas entre as séries, repetições e exercícios, como os treinos em circuito, o restpause, cluster training, intra-set rest e/ou inter-repetion rest, podem ter novas análises e, consequentemente, resultados interessantes a serem reportados.(AU)
The aim of the study was to provide a short communication about the adoption of density as a new metric to quantify strength training loads. We describe how quantify and highlighted the possible implications of density manipulation. Since considers the rest interval between sets - where important metabolic process such as phosphocreatine resynthesizes may occurs density may represent the magnitude of metabolic stress induced by training session. In this sense, is recommended that sports sciences coach's and researchers report the training density. Training techniques that manipulate the rest intervals between sets, repetitions, and exercises, such as circuit tra ining, rest pause, cluster training, intra-set rest, and/or inter-repetition rest may have new analysis, and consequently interesting results to be reported.(AU)
Assuntos
Humanos , Masculino , Feminino , Adulto , Fosfocreatina/metabolismo , Estresse Fisiológico , Treinamento Resistido/métodos , Aumento do Músculo EsqueléticoRESUMO
O treinamento de força (TF) proporciona adaptações centrais e morfológicas que influenciam no processo de produção de força. Em função destas adaptações é esperado que ocorram diferenças no desempenho de força entre homens com diferentes tempos de experiência no TF quanto testados em séries múltiplas. Assim, este estudo teve como objetivo comparar o número máximo de repetições (NMR) realizadas em 3 séries entre indivíduos com diferentes tempos de experiência no TF. Para isso, vinte e dois homens foram divididos em dois grupos de acordo com o tempo de experiência no TF. O Grupo Muito Experiente (GME) foi representado por homens com mais de 5 anos no TF. O Grupo Pouco Experiente (GPE) foi composto por homens com 1 a 6 meses de experiência no TF. Os grupos foram submetidos à realização do maior número de repetições em três séries a 80% de 1RM no exercício supino reto. Além disso, a duração média da repetição (DMR) foi registrada e comparada em cada série intra e inter grupos. Para as comparações foram utilizadas duas ANOVAs com única variável (NMR ou DMR) e dois fatores (fator 1 = experiência, fator 2 = série). Na análise do NMR foi detectada uma interação entre os fatores, sendo que o número máximo de repetições realizado pelo GME foi maior do que o GPE apenas na primeira série (p = 0,017). Quanto à DMR, não foram encontradas diferenças entre os grupos (p = 0,80) e séries (p= 0,06). Conclui-se que o tempo de experiência no TF interferiu na realização do número máximo de repetições apenas na primeira série... (AU)
Strength training (TF) provides central and morphological adaptations that influence the process of force production. Due to these adaptations, it is expected that differences in force performance occurred between men with different times of experience in the TF when tested in multiple series. Thus, this study had as objective to compare the maximum number of repetitions (NMR) performed in 3 sets between individuals with different times of experience in the TF. For this, twenty-two men were split into two groups according to the time of experience in the TF. The Very Experienced Group (GME) was represented by men older with at least 5 years in TF. The Little Experienced Group (GPE) was composed of men with 1 to 6 months of experience in TF. The groups were submitted to perform the highest number of repetitions in three sets at 80% of 1RM in the bench press exercise. In addition, mean repetition duration (DMR) was recorded and compared in each set and group. For the comparison, two ANOVAs with a single variable (NMR or DMR) and two factors (factor 1 = experience, factor 2 = set) were used. In the NMR analysis, an interaction between the factors was detected, and the NMR performed by the GME was higher than the GPE only at the first set (p = 0.017). Regarding DMR, no differences were found between groups (p = 0.80) and sets (p = 0,06). It is concluded that the time of experience in the TF interfered in the Performance of the maximum number of repetitions only at the first set...(AU)
Assuntos
Humanos , Masculino , Fosfocreatina , Força Muscular , Treino Aeróbico , Glicogênio , Hipertrofia , Educação Física e Treinamento , Exercício FísicoRESUMO
Evidences have suggested that the phosphoryl transfer network by the enzymatic activities of creatine kinase (CK), adenylate kinase (AK), pyruvate kinase (PK), and lactate dehydrogenase (LDH), shows new perspectives to understand some disturbances in the energy metabolism during bacterial infections. Thus, the aim of this study was to evaluate whether Staphylococcus aureus infection in mice could alter serum and cardiac activities of these enzymes and their association to disease pathophysiology. For that, we measured total leukocytes, lymphocytes and neutrophils (just 48â¯h of infection) that were lower in infected animals after 48 and 72â¯h in infected mice compared with negative control, while total protein and globulin plasma levels were higher after 72â¯h of infection. The serum CK activity was higher in infected animals 48 and 72â¯h post-infection compared to the control group, as well as observed for mitochondrial cardiac CK activity. The serum PK activity was higher in infected animals after 72â¯h of infection compared to the control group, and lower in the cardiac tissue. The cardiac AK activity was lower in infected animals 48â¯h and 72â¯h post-infection compared to the control group, while serum and cardiac LDH activities were higher. Based on these evidences, it is possible to conclude that the stimulation of CK activity exerts a key role as an attempt to maintain the bioenergetic homeostasis by the production of phosphocreatine to avoid a rapid fall on the concentrations of total adenosine triphosphate. In summary, the phosphoryl transfer network can be considered a pathway involved in the improvement on tissue and cellular energy homeostasis of S. aureus-infected mice.
Assuntos
Endocardite/metabolismo , Metabolismo Energético/fisiologia , Mitocôndrias Cardíacas/metabolismo , Infecções Estafilocócicas/sangue , Infecções Estafilocócicas/fisiopatologia , Staphylococcus aureus/metabolismo , Trifosfato de Adenosina/metabolismo , Adenilato Quinase/sangue , Adenilato Quinase/metabolismo , Animais , Creatina Quinase/sangue , Creatina Quinase/metabolismo , Creatina Quinase Mitocondrial/metabolismo , Modelos Animais de Doenças , Endocardite/microbiologia , Coração/microbiologia , Coração/fisiologia , Homeostase , Leucócitos , Fígado/microbiologia , Fígado/patologia , Linfócitos , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Neutrófilos , Fosfocreatina/metabolismo , Piruvato Quinase/sangue , Piruvato Quinase/metabolismo , Baço/microbiologia , Baço/patologia , Infecções Estafilocócicas/patologia , Staphylococcus aureus/enzimologiaRESUMO
PURPOSE: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). METHODS: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. RESULTS: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. CONCLUSIONS: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.
Assuntos
Isquemia Encefálica/metabolismo , Cardiotônicos/farmacologia , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Mitocondriais/metabolismo , Fosfocreatina/farmacologia , Traumatismo por Reperfusão/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose , Isquemia Encefálica/prevenção & controle , Caspase 3/metabolismo , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Humanos , Masculino , Fármacos Neuroprotetores/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Traumatismo por Reperfusão/prevenção & controleRESUMO
Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI).Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B [intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model], and group C [intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model]. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis.Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C.Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.(AU)
Assuntos
Animais , Masculino , Ratos , Fosfocreatina/administração & dosagem , Fosfocreatina/agonistas , Fosfocreatina/farmacologia , Isquemia Encefálica , Traumatismo por Reperfusão/induzido quimicamente , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X , Ratos Sprague-Dawley , Modelos Animais de DoençasRESUMO
Abstract Purpose: To observe the efficacy of phosphocreatine pre-administration (PCr-PA) on X-linked inhibitor of apoptosis protein (XIAP), the second mitochondia-derived activator of caspase (Smac) and apoptosis in the ischemic penumbra of rats with focal cerebral ischemia-reperfusion injury (CIRI). Methods: A total of 60 healthy male Sprague Dawley (SD) rats were randomly divided into three groups (n=20): group A (the sham operation group), group B <intraperitoneally injected with 20 mg/kg (10 mg/ml) of saline before preparing the ischemia-reperfusion (IR) model>, and group C <intraperitoneally injected with 20 mg/kg (10 mg/ml) of PCr immediately before preparing the IR model>. After 24 h for reperfusion, the neurological function was evaluated and the tissue was sampled to detect expression of XIAP, Smac and caspase-3 positive cells in the ischemic penumbra so as to observe the apoptosis. Results: Compared with group B, neurological deficit scores, numbers of apoptotic cells, expression of Smac,caspase-9 and the numbers of Caspase-3 positive cells were decreased while expression of XIAP were increased in the ischemic penumbra of group C. Conclusions: Phosphocreatine pre-administration may elicit neuroprotective effects in the brain by increasing expression of X-linked inhibitor of apoptosis protein, reducing expression of second mitochondia-derived activator of caspase, and inhibiting the apoptosis in the ischemic penumbra.
Assuntos
Humanos , Animais , Masculino , Ratos , Fosfocreatina/farmacologia , Cardiotônicos/farmacologia , Traumatismo por Reperfusão/metabolismo , Isquemia Encefálica/metabolismo , Proteínas Mitocondriais/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo , Distribuição Aleatória , Isquemia Encefálica/prevenção & controle , Ratos Sprague-Dawley , Apoptose/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Modelos Animais de Doenças , Avaliação Pré-Clínica de Medicamentos , Proteínas Reguladoras de Apoptose , Caspase 3/metabolismoRESUMO
Cytosolic and mitochondrial creatine kinases (CK), through the creatine kinase-phosphocreatine (CK/PCr) system, provide a temporal and spatial energy buffer to maintain cellular energy homeostasis. However, the effects of bacterial infections on the kidney remain poorly understood and are limited only to histopathological analyses. Thus, the aim of this study was to investigate the involvement of cytosolic and mitochondrial CK activities in renal energetic homeostasis in silver catfish experimentally infected with Aeromonas caviae. Cytosolic CK activity decreased in infected animals, while mitochondrial CK activity increased compared to uninfected animals. Moreover, the activity of the sodium-potassium pump (Na+, K+-ATPase) decreased in infected animals compared to uninfected animals. Based on this evidence, it can be concluded that the inhibition of cytosolic CK activity by A. caviae causes an impairment on renal energy homeostasis through the depletion of adenosine triphosphate (ATP) levels. This contributes to the inhibition of Na+, K+-ATPase activity, although the mitochondrial CK activity acted in an attempt to restore the cytosolic ATP levels through a feedback mechanism. In summary, A. caviae infection causes a severe energetic imbalance in infected silver catfish, which may contribute to disease pathogenesis.
Assuntos
Aeromonas caviae/patogenicidade , Peixes-Gato/microbiologia , Creatina Quinase Mitocondrial/metabolismo , Citosol/metabolismo , Metabolismo Energético/fisiologia , Doenças dos Peixes/microbiologia , Infecções por Bactérias Gram-Negativas/veterinária , Rim/metabolismo , Adenosina Trifosfatases/metabolismo , Trifosfato de Adenosina/metabolismo , Animais , Brasil , Creatina Quinase/metabolismo , Citosol/enzimologia , Modelos Animais de Doenças , Doenças dos Peixes/patologia , Infecções por Bactérias Gram-Negativas/microbiologia , Infecções por Bactérias Gram-Negativas/patologia , Homeostase , Rim/microbiologia , Rim/patologia , Mitocôndrias/enzimologia , Mitocôndrias/metabolismo , Fosfocreatina/metabolismo , Fosforilação , ATPase Trocadora de Sódio-Potássio/metabolismoRESUMO
Creatine/phosphorylcreatine (PCr) responses to creatine supplementation may be modulated by age, diet, and tissue, but studies assessing this possibility are lacking. Therefore we aimed to determine whether PCr responses vary as a function of age, diet, and tissue. Fifteen children, 17 omnivorous and 14 vegetarian adults, and 18 elderly individuals ("elderly") participated in this study. Participants were given placebo and subsequently creatine (0.3 g·kg-1·day-1) for 7 days in a single-blind fashion. PCr was measured through phosphorus magnetic resonance spectroscopy (31P-MRS) in muscle and brain. Creatine supplementation increased muscle PCr in children (P < 0.0003) and elderly (P < 0.001), whereas the increase in omnivores did not reach statistically significant difference (P = 0.3348). Elderly had greater PCr increases than children and omnivores (P < 0.0001 for both), whereas children experienced greater PCr increases than omnivores (P = 0.0022). In relation to diet, vegetarians (P < 0.0001), but not omnivores, had significant increases in muscle PCr content. Brain PCr content was not affected by creatine supplementation in any group, and delta changes in brain PCr (-0.7 to +3.9%) were inferior to those in muscle PCr content (+10.3 to +27.6%; P < 0.0001 for all comparisons). PCr responses to a standardized creatine protocol (0.3 g·kg-1·day-1 for 7 days) may be affected by age, diet, and tissue. Whereas creatine supplementation was able to increase muscle PCr in all groups, although to different extents, brain PCr was shown to be unresponsive overall. These findings demonstrate the need to tailor creatine protocols to optimize creatine/PCr accumulation both in muscle and in brain, enabling a better appreciation of the pleiotropic properties of creatine.NEW & NOTEWORTHY A standardized creatine supplementation protocol (0.3 g·kg-1·day-1 for 7 days) effectively increased muscle, but not brain, phosphorylcreatine. Older participants responded better than younger participants whereas vegetarians responded better than omnivores. Responses to supplementation are thus dependent on age, tissue, and diet. This suggests that a single "universal" protocol, originally designed for increasing muscle creatine in young individuals, may lead to heterogeneous muscle responses in different populations or even no responses in tissues other than skeletal muscle.
Assuntos
Creatina/administração & dosagem , Fosfocreatina/metabolismo , Adulto , Idoso , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Criança , Dieta , Suplementos Nutricionais , Feminino , Humanos , Espectroscopia de Ressonância Magnética/métodos , Masculino , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Método Simples-CegoRESUMO
OBJECTIVE: To determine associations between patient and clinical factors with postnatal brain metabolism in term neonates with congenital heart disease (CHD) via the use of quantitative magnetic resonance spectroscopy. STUDY DESIGN: Neonates with CHD were enrolled prospectively to undergo pre- and postoperative 3T brain magnetic resonance imaging. Short-echo single-voxel magnetic resonance spectroscopy of parietal white matter was used to quantify metabolites related to brain maturation (n-acetyl aspartate, choline, myo- inositol), neurotransmitters (glutamate and gamma-aminobutyric acid), energy metabolism (glutamine, citrate, glucose, and phosphocreatine), and injury/apoptosis (lactate and lipids). Multivariable regression was performed to search for associations between (1) patient-specific/prenatal/preoperative factors with concurrent brain metabolism and (2) intraoperative and postoperative factors with postoperative brain metabolism. RESULTS: A total of 83 magnetic resonance images were obtained on 55 subjects. No patient-specific, prenatal, or preoperative factors associated with concurrent metabolic brain dysmaturation or elevated lactate could be identified. Chromosome 22q11 microdeletion and age at surgery were predictive of altered concurrent white matter phosphocreatine (P < .0055). The only significant intraoperative association found was increased deep hypothermic circulatory arrest time with reduced postoperative white matter glutamate and gamma-aminobutyric acid (P < .0072). Multiple postoperative factors, including increased number of extracorporeal membrane oxygenation days (P < .0067), intensive care unit, length of stay (P < .0047), seizures in the intensive care unit (P < .0009), and home antiepileptic use (P < .0002), were associated with reduced postoperative white matter n-acetyl aspartate. CONCLUSION: Multiple postoperative factors were found to be associated with altered brain metabolism in term infants with CHD, but not patient-specific, preoperative, or intraoperative factors.
Assuntos
Encéfalo/metabolismo , Cardiopatias Congênitas/cirurgia , Imageamento por Ressonância Magnética/métodos , Espectroscopia de Ressonância Magnética/métodos , Ácido Aspártico/análogos & derivados , Ácido Aspártico/metabolismo , Biomarcadores/metabolismo , Peso ao Nascer , Encéfalo/diagnóstico por imagem , Estudos de Coortes , Feminino , Idade Gestacional , Glutamina/metabolismo , Cardiopatias Congênitas/diagnóstico , Cardiopatias Congênitas/mortalidade , Humanos , Recém-Nascido , Ácido Láctico/metabolismo , Masculino , Monitorização Intraoperatória/métodos , Análise Multivariada , Fosfocreatina/metabolismo , Cuidados Pré-Operatórios/métodos , Prognóstico , Estudos Prospectivos , Análise de Regressão , Medição de Risco , Taxa de Sobrevida , Nascimento a Termo , Resultado do TratamentoRESUMO
INTRODUCTION: It has been suggested that creatine supplementation is safe and effective for treating idiopathic inflammatory myopathies, but no pediatric study has been conducted to date. The objective of this study was to examine the efficacy and safety of creatine supplementation in juvenile dermatomyositis (JDM) patients. METHODS: In this study, JDM patients received placebo or creatine supplementation (0.1 g/kg/day) in a randomized, crossover, double-blind design. Subjects were assessed at baseline and after 12 weeks. The primary outcome was muscle function. Secondary outcomes included body composition, aerobic conditioning, health-related quality of life, and muscle phosphocreatine (PCr) content. Safety was assessed by laboratory parameters and kidney function measurements. RESULTS: Creatine supplementation did not affect muscle function, intramuscular PCr content, or any other secondary outcome. Kidney function was not affected, and no side effects were reported. CONCLUSIONS: Twelve weeks of creatine supplementation in JDM patients were well-tolerated and free of adverse effects, but treatment did not affect muscle function, intramuscular PCr, or any other parameter.
Assuntos
Creatina/uso terapêutico , Dermatomiosite/dietoterapia , Suplementos Nutricionais , Adolescente , Composição Corporal , Densidade Óssea , Criança , Estudos Cross-Over , Citocinas/sangue , Dermatomiosite/patologia , Método Duplo-Cego , Ingestão de Alimentos/fisiologia , Exercício Físico , Feminino , Humanos , Imageamento por Ressonância Magnética , Espectroscopia de Ressonância Magnética , Masculino , Músculo Esquelético/metabolismo , Fosfocreatina/metabolismo , Qualidade de Vida , Sensibilidade e Especificidade , Inquéritos e Questionários , Escala Visual Analógica , Adulto JovemRESUMO
Levan productivity of Bacillus subtilis Natto was evaluated in submerged culture varying the pH, temperature and culture time, using factorial design and response surface methodology. The characterization of levan molecular weight was performed by HPSEC and its antitumor activity against HepG2 cells using metabolomic approach was also evaluated. At first, the variables investigated, as well as their interactions, demonstrated significant effect. Further, a second design using the same variables at different levels was developed. Thus, according to the model, an optimized value corresponding to 5.82 g.L⻹.h⻹ was achieved at pH 8, 39.5°C in 21 hours, the highest value reported so far. After analysis by HPSEC, two molecular weights were obtained corresponding to 72.37 and 4146 kDa. The levan promoted an increase of acetate, alanine, lactate and phosphocreatine in HepG2 cells suggesting an alteration in the bioenergetics pathways and cellular homeostasis by intracellular accumulation of lactate, justifying its antitumor activity.
Assuntos
Antineoplásicos/farmacologia , Bacillus subtilis/metabolismo , Metabolismo Energético/efeitos dos fármacos , Frutanos/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Metabolômica , Ácido Acético/metabolismo , Alanina/metabolismo , Antineoplásicos/metabolismo , Fermentação , Frutanos/metabolismo , Células Hep G2 , Humanos , Concentração de Íons de Hidrogênio , Ácido Láctico/metabolismo , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Metabolômica/métodos , Peso Molecular , Fosfocreatina/metabolismo , Temperatura , Fatores de TempoRESUMO
Water pollution by agrochemicals is currently one of the most critical problems for the conservation of aquatic ecosystems. Glyphosate [N-(phosphonomethyl) glycine); PMG] is the main broad-spectrum post emergence herbicide used for the control of a wide range of pests in soybean crops. Adenylate energy charge (AEC) reflects the energy balance of the cells, a measure of the energy available from the adenylate pool: adenosine triphosphate (ATP), adenosine diphosphate (ADP) and adenosine monophosphate (AMP). Background adenylates, phosphagens and the AEC index of two year old Odontesthes bonariensis were determined in some tissues by HPLC, and the impact on subcellular energy balance of sublethal glyphosate-based herbicide exposure was analyzed. The doses used were 0 (control tank), 1 or 10mg PMGL(-1), trials were carried out during 15 days. AEC values in brain, liver and muscle from control fish were 0.37 ± 0.02, 0.49 ± 0.05 and 0.56 ± 0.03, respectively (means ± SEM). While brain ATP concentrations were undetectable (hence low values of AEC), the muscle tissue showed the highest concentrations of the more energetic molecules: 0.18 µmole ATP g(-1) and 8 µmole phosphocreatine g(-1) (PCrg(-1)). In the brain, no significant changes were detected in exposed fish compared to controls. Instead, in both the liver and muscle of animals exposed to the highest concentration of the herbicide, significant changes in the AEC (reduction of 26% and 15%, p<0.05) with respect to the control group were determined. Chronic exposure (15 days) of Odontesthes bonariensis to 1 and 10mgL(-1) of formulated glyphosate did not affect brain AEC. However, the highest concentration of the herbicide produced a significant decrease in liver and muscle AEC manifesting adverse sublethal effects on the energy metabolism. These results suggest the usefulness of AEC as a biomarker of fish glyphosate exposure.
Assuntos
Nucleotídeos de Adenina/metabolismo , Metabolismo Energético/efeitos dos fármacos , Glicina/análogos & derivados , Herbicidas/toxicidade , Smegmamorpha , Poluentes Químicos da Água/toxicidade , Animais , Biomarcadores/metabolismo , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Relação Dose-Resposta a Droga , Glicina/toxicidade , Fígado/efeitos dos fármacos , Fígado/metabolismo , Músculos/metabolismo , Fosfocreatina/metabolismo , Smegmamorpha/metabolismo , GlifosatoRESUMO
Adenosine triphosphate is the present energy currency in the body, and is used in various cellular and indispensable processes for the maintenance of cell homeostasis. The regeneration mechanisms of adenosine triphosphate, from the product of its hydrolysis - adenosine diphosphate - are therefore necessary. Phosphocreatine is known as its quickest form of regeneration, by means of the enzyme creatine kinase. Thus, the primary function of this system is to act as a temporal energy buffer. Nevertheless, over the years, several other functions were attributed to phosphocreatine. This occurs as various isoforms of creatine kinase isoforms have been identified with a distinct subcellular location and functionally coupled with the sites that generate and use energy, in the mitochondria and cytosol, respectively. The present study discussed the central and complex role that the phosphocreatine system performs in energy homeostasis in muscle cells, as well as its alterations in pathological conditions.
Assuntos
Homeostase/fisiologia , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Fosfocreatina/metabolismo , Creatina Quinase/metabolismo , Metabolismo Energético/fisiologia , HumanosRESUMO
Adenosine triphosphate is the present energy currency in the body, and is used in various cellular and indispensable processes for the maintenance of cell homeostasis. The regeneration mechanisms of adenosine triphosphate, from the product of its hydrolysis – adenosine diphosphate – are therefore necessary. Phosphocreatine is known as its quickest form of regeneration, by means of the enzyme creatine kinase. Thus, the primary function of this system is to act as a temporal energy buffer. Nevertheless, over the years, several other functions were attributed to phosphocreatine. This occurs as various isoforms of creatine kinase isoforms have been identified with a distinct subcellular location and functionally coupled with the sites that generate and use energy, in the mitochondria and cytosol, respectively. The present study discussed the central and complex role that the phosphocreatine system performs in energy homeostasis in muscle cells, as well as its alterations in pathological conditions.
A adenosina trifosfato é a moeda corrente de energia no organismo, sendo utilizada em diversos processos celulares e indispensável para a manutenção da homeostase celular. Mecanismos de regeneração da adenosina trifosfato, a partir de seu produto de hidrólise – a adenosina difosfato – são, dessa forma, necessários. A fosfocreatina é conhecidamente sua fonte mais rápida de regeneração, por meio da enzima creatina quinase. Assim, a principal função desse sistema é atuar como um tampão temporal de energia. Entretanto, ao longo dos anos, diversas outras funções foram atribuídas à fosfocreatina. Isso ocorreu à medida que foram identificadas diversas isoformas da creatina quinase com localização subcelular distinta e acopladas de forma funcional aos sítios geradores e utilizadores de energia, na mitocôndria e citosol, respectivamente. O presente trabalho discutiu o papel central e complexo que o sistema da fosfocreatina desempenha na homeostase energética nas células musculares, bem como suas alterações em quadros patológicos.
Assuntos
Humanos , Homeostase/fisiologia , Músculo Esquelético/metabolismo , Miocárdio/metabolismo , Fosfocreatina/metabolismo , Creatina Quinase/metabolismo , Metabolismo Energético/fisiologiaRESUMO
Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.
Assuntos
Doença de Huntington/metabolismo , Espectroscopia de Ressonância Magnética , Doenças Talâmicas/metabolismo , Tálamo/fisiopatologia , Adolescente , Adulto , Idoso , Ácido Aspártico/análogos & derivados , Ácido Aspártico/análise , Estudos de Casos e Controles , Creatina/análise , Deutério , Dipeptídeos/análise , Feminino , Glicerilfosforilcolina/análise , Humanos , Masculino , Pessoa de Meia-Idade , Atividade Motora , Fosfocreatina/análise , Fosforilcolina/análise , Doenças Talâmicas/diagnóstico , Repetições de Trinucleotídeos , Adulto JovemRESUMO
Huntington's disease (HD) is a neurologic disorder that is not completely understood; its fundamental physiological mechanisms and chemical effects remain somewhat unclear. Among these uncertainties, we can highlight information about the concentrations of brain metabolites, which have been widely discussed. Concentration differences in affected, compared to healthy, individuals could lead to the development of useful tools for evaluating the progression of disease, or to the advance of investigations of different/alternative treatments. The aim of this study was to compare the thalamic concentration of metabolites in HD patients and healthy individuals using magnetic resonance spectroscopy. We used a 2.0-Tesla magnetic field, repetition time of 1500 ms, and echo time of 135 ms. Spectra from 40 adult HD patients and 26 control subjects were compared. Quantitative analysis was performed using the LCModel method. There were statistically significant differences between HD patients and controls in the concentrations of N-acetylaspartate+N-acetylaspartylglutamate (NAA+NAAG; t-test, P<0.001), and glycerophosphocholine+phosphocholine (GPC+PCh; t-test, P=0.001) relative to creatine+phosphocreatine (Cr+PCr). The NAA+NAAG/Cr+PCr ratio was decreased by 9% and GPC+PCh/Cr+PCr increased by 17% in patients compared with controls. There were no correlations between the concentration ratios and clinical features. Although these results could be caused by T1 and T2 changes, rather than variations in metabolite concentrations given the short repetition time and long echo time values used, our findings point to thalamic dysfunction, corroborating prior evidence.
Assuntos
Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Adulto Jovem , Doença de Huntington/metabolismo , Espectroscopia de Ressonância Magnética , Doenças Talâmicas/metabolismo , Tálamo/fisiopatologia , Ácido Aspártico/análise , Ácido Aspártico/análogos & derivados , Estudos de Casos e Controles , Creatina/análise , Deutério , Dipeptídeos/análise , Glicerilfosforilcolina/análise , Atividade Motora , Fosfocreatina/análise , Fosforilcolina/análise , Repetições de Trinucleotídeos , Doenças Talâmicas/diagnósticoRESUMO
OBJECTIVE: To investigate the efficacy and safety of creatine supplementation in fibromyalgia patients. METHODS: A 16-week, randomized, double-blind, placebo-controlled, parallel-group trial was conducted. Fibromyalgia patients were randomly assigned to receive either creatine monohydrate or placebo in a double-blind manner. The patients were evaluated at baseline and after 16 weeks. Muscle function, aerobic conditioning, cognitive function, quality of sleep, quality of life, kidney function, and adverse events were assessed. Muscle phosphorylcreatine content was measured through (31) P magnetic resonance spectroscopy. RESULTS: After the intervention, the creatine group presented higher muscle phosphorylcreatine content when compared with the placebo group (+80.3% versus -2.7%; P = 0.04). Furthermore, the creatine group presented greater muscle strength than the placebo group in the leg press and chest press exercises (+9.8% and +1.2% for creatine versus -0.5% and -7.2% for placebo, respectively; P = 0.02 and P = 0.002, respectively). Isometric strength was greater in the creatine group than in the placebo group (+6.4% versus -3.2%; P = 0.007). However, no general changes were observed in aerobic conditioning, pain, cognitive function, quality of sleep, and quality of life. Food intake remained unaltered and no side effects were reported. CONCLUSION: Creatine supplementation increased intramuscular phosphorylcreatine content and improved lower- and upper-body muscle function, with minor changes in other fibromyalgia features. These findings introduce creatine supplementation as a useful dietary intervention to improve muscle function in fibromyalgia patients.
Assuntos
Creatina/administração & dosagem , Suplementos Nutricionais , Fibromialgia/diagnóstico , Fibromialgia/tratamento farmacológico , Adulto , Creatina/metabolismo , Método Duplo-Cego , Feminino , Fibromialgia/metabolismo , Humanos , Pessoa de Meia-Idade , Fosfocreatina/metabolismoRESUMO
Physical activity and fitness are associated with a lower prevalence of chronic diseases, such as heart disease, cancer, high blood pressure, and diabetes. This review discusses the body's response to an acute bout of exercise and long-term physiological adaptations to exercise training with an emphasis on endurance exercise. An overview is provided of skeletal muscle actions, muscle fiber types, and the major metabolic pathways involved in energy production. The importance of adequate fluid intake during exercise sessions to prevent impairments induced by dehydration on endurance exercise, muscular power, and strength is discussed. Physiological adaptations that result from regular exercise training such as increases in cardiorespiratory capacity and strength are mentioned. The review emphasizes the cardiovascular and metabolic adaptations that lead to improvements in maximal oxygen capacity.